This application proposes and investigation of the functional relationship between adenosine deaminase and the adenosine deaminase complexing proteins. Based on previous observations, it is suggested that humans have a system for specifically removing monomeric adenosine deaminase from the plasma. The rabbit which appears to be a good model in which to study the complexing proteins will be used to test this hypothesis. Initially, different molecular forms of adenosine deaminase will be injected intravenously into rabbits. The sites of uptake and mechanism by which monomeric and high-molecular weight adenosine deaminase is removed from circulation will be investigated. A preliminary study indicates that monomeric adenosine deaminase, filtered by the glomerulus, is taken up by cells lining the proximal renal tubules. Experiments with the isolated perfused kidney will be used to determine if complexing protein is involved in this process. The infusion study and other results raise the posssibility that complexing protein, bound to the surface of kidney epithelial cells, may act as a receptor for adenosine deaminase. The interaction of monomeric adenosine deaminase with cultured epithelial-like cell lines derived from kidney (probably from monkey) and human fibroblasts will be investigated to evaluate this possibility. This study may provide the basis for a new method of enzyme replacement therapy for adenosine deaminase deficient-combined immune deficient infants. Adenosine deaminase appears to play a vital role in the development of the thymus. The different forms fo adenosine deaminase found in human thymus will be purified and characterized. Purifications will be accomplished using a variety of immunoadsorbant and affinity column chromatography bed materials prepared for this project. The propeties of monomeric adenosine deaminase and enzyme associated with complexing protein will be compared. This study may help to determine if the complexing proteins, by modifying the location or kinetic properties of adenosine deaminase, help to protect the thymus from deoxyadenosine.